Gut Bifidobacterium longum is Associated with Better Native Liver Survival in Patients with Biliary Atresia

Abstract

Background & AimsThe gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbiota signature in the early life of patients with BA and to analyze its influence on long-term outcomes. MethodsFecal samples (n=42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing (NGS) and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed. ResultsIn the 16S rRNA NGS fecal microbial analysis, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyl transferase level after KPE (P<0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (P<0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI: 0.03-0.83, P=0.029). Shotgun metagenomic sequencing also revealed that BA patients with detectable B. longum had reduced total and direct bilirubin after KPE. ConclusionThe gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes. Impact and implicationsB. longum is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with BA, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with BA.